Do You Consider Medications to Treat Obesity?

Robert F. Kushner, MD

Do you consider using medications when treating patients for obesity? If you answered no, it's time to make a change in your practice. Our current understanding of obesity as a chronic, progressive, and relapsing disease, just like type 2 diabetes, is useful in making the mindset shift toward a medical treatment model.

Obesity is now considered a disease of energy dysregulation whereby altered biological signals and the environment contribute to weight gain and accumulating excess body fat. As with diabetes, we need to use a variety of approaches to help our patients better manage their obesity. Counseling around choosing a calorie-controlled healthy diet, being more physically activity, and using strategies for behavior change are foundational steps for all patients seeking treatment for obesity.

However, lifestyle management is often not enough for many of our patients, who continue to struggle with their weight and have coexisting medical problems. It is no longer acceptable to simply tell patients to "just try harder" when more effective adjunctive treatments are available. Rather, you should consider whether the patient is a candidate for prescribing a US Food and Drug Administration (FDA)–approved medication for chronic weight management.

How Do Anti-obesity Medications Work?

There are currently five medications approved by the FDA for long-term use — orlistat (Xenical), phentermine/topiramate (Qsymia), naltrexone-bupropion (Contrave), liraglutide (Saxenda), and semaglutide (Wegovy) — and one is approved for short-term use (phentermine). All of these drugs, except orlistat, alter the patient's appetite perception by modifying biological signaling in the brain. Although individual responses vary, patients may feel less hungry, feel fuller after a meal and more content between meals, and have reduced cravings and less thoughts of food. By controlling appetite, the patient is able to adhere to a lower-calorie diet more consistently. For this reason, patients taking medications lose 5%-12% more weight than those following a lifestyle plan alone.

Who Are Candidates for Anti-obesity Medications?

Anti-obesity medications are approved for patients with a body mass index ≥ 30 or a body mass index ≥ 27 with a comorbidity. Additional considerations include patients who are actively engaged in self-care, attentive to their diet but struggling to make dietary changes, are unable to lose or maintain a lower body weight, and have a desire for improved health.

Which medication to choose depends on existing comorbidities, side effects, patient preference, insurance coverage, and cost (if paid out of pocket).

Concomitant treatment of comorbidities is also an important factor. For example, a patient with diabetes would benefit from use of a glucagon like peptide 1 receptor agonist (GLP-1 RA), such as liraglutide or semaglutide, because they are incretin hormone agents used to treat diabetes. Similarly, a patient with a history of migraine headaches may benefit from phentermine-topiramate because topiramate is also approved for migraine prophylaxis. Each medication has its own unique titration schedule, so clinicians need to become familiar with dosing instructions. Regardless of the medication selected, the patient needs to be informed that treatment is intended for long-term use because discontinuation will result in reemergence of increased appetite and weight regain.

How Do Patients Feel About Taking Medications for Chronic Weight Management?

For some patients, there is a stigma around taking weight loss drugs, a concern that they will be perceived as being unable or too weak to manage their weight on their own. This is born of the misbelief that obesity is entirely due to overeating and lack of physical activity. Failure to control body weight is a sign of laziness, lack of personal responsibility, and gluttony. Thus, it follows that taking a medication is the "easy way out."

It is important to convey to the patient that excessive body weight is considered a medical condition, requiring supportive care such as lifestyle counseling, referral to a registered dietitian or health psychologist, prescription of a medication, or consideration of bariatric surgery. Anti-obesity medications assist a patient with appetite control and make dietary adherence more successful.

What Medications Are on the Horizon?

We are entering a new phase of treatment for obesity that is harnessing the appetite-controlling effects of naturally occurring, nutrient-stimulated gastrointestinal and pancreatic hormones that include GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin.

Semaglutide, a second-generation GLP-1 RA, was approved for chronic weight management in 2021 after publication of the STEP randomized controlled trials. In STEP 1, average weight loss at 68 weeks was 15% vs 2.4% with placebo. Semaglutide was also found to be 2.5 times more effective than the first-generation drug liraglutide.

Average body weight reduction with tirzepatide, a new dual GLP-1 and GIP RA, reached 21% after 72 weeks on the 15-mg dose.^,Additional combination agents and mono-, dual-, and tri-agonists that contain these hormones are currently under investigation.

Putting It All Together

Similar to other chronic medical conditions, we need to use a multi-treatment strategy to help our patients achieve best outcomes. For obesity management, this includes providing lifestyle counseling on choosing a healthy calorie-controlled diet, increasing physical activity, and strategies to implement positive behavioral changes. For many patients, adding an anti-obesity medication to the regimen will enable patients to be more successful in losing weight and for long-term weight maintenance. It is incumbent upon the medical provider to become familiar with the use of available and emerging agents.

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